The mammalian eye includes a cornea, a fluid-filled anterior chamber, a lens, a fluid-filled posterior chamber, and a photosensitive retina. The designations “anterior” and “posterior” are with reference to the lens. Light enters the eye through the cornea, passes through the anterior chamber and is focused onto the retina by the lens. The retina is composed of numerous types of cells including photosensitive rods, that are responsible for night vision, and photosensitive cones that are responsible for high acuity day vision. The rods and cones communicate with neurons in the retina that transmit nerve impulses to the visual centers of the brain where this information is processed to generate the perception of visual information. For example, rods and cones communicate with bipolar cells, that, in turn, communicate with ganglion cells that transmit nerve impulses to the brain.
Half of all blindness is caused by damage or disease of the retina (Zrenner (2002) Science 295(5557):1022-26). Death of photoreceptors has many causes, some of which are the results of known, underlying, genetic mutations, while others are of unknown cause. In the condition known as retinitis pigmentosa, the rods degenerate first and result in loss of night vision, and later the cones degenerate, resulting in total blindness. In the condition known as age-related macular degeneration, the cones degenerate, and since they are necessary for high acuity vision, these individuals also become functionally blind. In both diseases the non-photoreceptive neurons, such as the bipolar and ganglion cells, remain largely intact (Santos et al. (1997) Arch. Ophthamol. 115:511-5; Kim et al. (2002) Retina 22:464-70; Kim et al. (2002) Retina 22:471-7). Due to the many applications of lasers and the increasing use in the military, laser eye injuries that destroy the retinal pigmented epithelium and light-sensitive photoreceptors are a growing problem (Barkana & Belkin (2000) Surv. Ophthalmol. 44(6):459-478). The retinal pigmented epithelium is located between the photoreceptors and the choroid of the eye. Certain laser eye injuries preserve the functionality of the retinal neurons, so that the use of vision prostheses become a viable option (e.g., krypton laser damage, Weiland et al. (1999) Graefe's Arch. Clin. Exp. Ophthalmol. 237:1007-13).
There are currently no treatments for most eye injuries and diseases that cause the destruction and degeneration of photoreceptors. There have been attempts, however, to develop a retinal prosthesis by the implantation of multiple active electrodes which sense light impinging on the retina and generate corresponding electrical signals that stimulate the healthy retinal neurons in the eye (see, e.g., Dagnelie & Massof (1996) IEEE Spectrum, May 22-29; Chase (1999) Technol. Rev. 102:44-48; Haystead (1999) Vision Systems Design 4(6):31-36; Chow et al. (2002) J. Rehab. Res. Dev. 39(3):313-22; Humayun et al. (2003) Vision Res. 43(24):2573-81). Implanted electrode arrays have significant limitations, however, such as power dissipation, incompatibility with surrounding biological tissues, low density of photocells in the electrode arrays, and the lack of knowledge about the neural interconnections to the bipolar and ganglion cells, and the type of stimulation required to mimic retinal signal processing (Liu et al. (2000) IEEE J. Solid-State Circuits, 35(10):1487-1497; Zrenner (2002) Science 295(5557):1022-26).
Thus, there is a continuing need for less invasive prosthetic devices capable of stimulating, inhibiting, or otherwise modulating, the activity of retinal neurons, in damaged and diseased retinas in which the photosensitive cells are functionally impaired, in order to generate a pattern of nerve impulses that are transmitted to the visual centers of the brain to yield visual information. There is also a need for manipulating the mammalian retina to promote health, for example, by stimulating retinal cells to take up molecules such as nucleic acids, proteins, and nutrients.